Variant chrX-7257367-ACCT-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP6_Very_StrongBS2

The NM_001320752.2(STS):c.259+8_259+10del variant causes a splice donor 5th base, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0073 in 1,210,421 control chromosomes in the GnomAD database, including 37 homozygotes. There are 2,775 hemizygotes in GnomAD. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0058 ( 4 hom., 170 hem., cov: 24)

Exomes 𝑓: 0.0075 ( 33 hom. 2605 hem. )

Consequence

STS
NM_001320752.2 splice_donor_5th_base, intron

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.0360

Variant links:

Genes affected

STS (HGNC:11425): (steroid sulfatase) This gene encodes a multi-pass membrane protein that is localized to the endoplasmic reticulum. It belongs to the sulfatase family and hydrolyzes several 3-beta-hydroxysteroid sulfates, which serve as metabolic precursors for estrogens, androgens, and cholesterol. Mutations in this gene are associated with X-linked ichthyosis (XLI). Alternatively spliced transcript variants resulting from the use of different promoters have been described for this gene (PMID:17601726). [provided by RefSeq, Mar 2016]

STS links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP6

Variant X-7257367-ACCT-A is Benign according to our data. Variant chrX-7257367-ACCT-A is described in ClinVar as [Likely_benign]. Clinvar id is 445931.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-7257367-ACCT-A is described in Lovd as [Likely_benign].

BS2

High Homozygotes in GnomAd4 at 4 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STS	NM_001320752.2 linkuse as main transcript	c.259+8_259+10del		splice_donor_5th_base_variant, intron_variant		ENST00000674429.1	NP_001307681.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STS	ENST00000674429.1 linkuse as main transcript	c.259+8_259+10del		splice_donor_5th_base_variant, intron_variant			NM_001320752.2	ENSP00000501534	P1

Frequencies

GnomAD3 genomes

AF:

0.00579

AC:

651

AN:

112381

Hom.:

Cov.:

AF XY:

0.00492

AC XY:

170

AN XY:

34557

show subpopulations

Gnomad AFR

AF:

0.000871

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00235

Gnomad ASJ

AF:

0.00528

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00182

Gnomad FIN

AF:

0.0127

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00938

Gnomad OTH

AF:

0.00199

GnomAD3 exomes

AF:

0.00605

AC:

1107

AN:

182866

Hom.:

AF XY:

0.00557

AC XY:

375

AN XY:

67366

show subpopulations

Gnomad AFR exome

AF:

0.000914

Gnomad AMR exome

AF:

0.00139

Gnomad ASJ exome

AF:

0.00321

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00110

Gnomad FIN exome

AF:

0.0165

Gnomad NFE exome

AF:

0.00882

Gnomad OTH exome

AF:

0.00664

GnomAD4 exome

AF:

0.00745

AC:

8182

AN:

1097990

Hom.:

AF XY:

0.00717

AC XY:

2605

AN XY:

363350

show subpopulations

Gnomad4 AFR exome

AF:

0.000909

Gnomad4 AMR exome

AF:

0.00168

Gnomad4 ASJ exome

AF:

0.00392

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00107

Gnomad4 FIN exome

AF:

0.0152

Gnomad4 NFE exome

AF:

0.00841

Gnomad4 OTH exome

AF:

0.00573

GnomAD4 genome

AF:

0.00579

AC:

651

AN:

112431

Hom.:

Cov.:

AF XY:

0.00491

AC XY:

170

AN XY:

34617

show subpopulations

Gnomad4 AFR

AF:

0.000869

Gnomad4 AMR

AF:

0.00234

Gnomad4 ASJ

AF:

0.00528

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00182

Gnomad4 FIN

AF:

0.0127

Gnomad4 NFE

AF:

0.00939

Gnomad4 OTH

AF:

0.00197

Alfa

AF:

0.00743

Hom.:

Bravo

AF:

0.00471

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Jun 15, 2017	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 02, 2024	- -

X-linked ichthyosis with steryl-sulfatase deficiency

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Jul 21, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over